Fig. 2

Interaction between sclerostin and Wnt signaling. a Soluble Wnt ligands bind to a receptor complex consisting of Frizzled and LDL-receptor-related protein 5/6 (LRP-5/6), and the receptor complex interacts with the phosphoprotein Dishevelled (Dsh). Wnt ligand binding and activation of Dsh result in the relocation of Axin followed by disassembly of the β-catenin degradation complex. Then, unphosphorylated β-catenin accumulates, translocates into the nucleus, and modifies gene transcription. b In the presence of sclerostin, a soluble Wnt inhibitor, Wnt ligands are blocked from binding the LRP-5/6-Frizzled receptor complex which in turn allows activation of the β-catenin degradation complex (CK-APCGSK3-Axin complex). Phosphorylation of β-catenin by GSK3 and CK1 blocks the translocation of β-catenin into the nucleus and increases β-catenin degradation via proteolysis [15]